Book of Abstracts: Albany 2011
June 14-18 2011
©Adenine Press (2010)
Exploring Folding Funnel of Villin Headpiece Using Replica Exchange Molecular Dynamics and Amber United Atom Model
Understanding protein folding has been a scientifically and computationally challenging task till date. The question, “How does an amino acid sequence dictate the structure of a protein?” has been of major interest and different theories have been put forward to answer it. Despite the success of deriving the 3 D structure of a protein (for example see 1, 2) from our conventional understanding of the preferential interactions between certain amino acids, recently questions have been raised regarding the use of statistical potentials and preferential interactions (3). Reaching the experimental time scale of millisecond is a grand challenge for protein folding simulations. The major challenges involved in the use of molecular dynamics (MD) simulations are to explore folding landscape for fast folding proteins and give an atomic level understanding of the folding process (4). The advanced methodologies like REMD (5) and Coarse-grained MD and computational power enable one to carry out long simulations. The advanced methods like REMD have significantly contributed to the understanding of the folding landscape of various ultrafast folding proteins. The advancement of force field to handle Coarse Grained models over all atom model system may be needed in achieving the goal of very long time scale folding simulation. Here an attempt has been made to reach the multi-microsecond simulation time scale by carrying out folding simulation on a fast folding three Helix bundle protein. A combination of REMD and Amber United atom model (6) has been employed. Two folding simulations based on REMD have been carried out on Villin headpiece (PDB code 1VII), a 36-residue small three Helix bundle protein (7) starting with an extended conformation. The protein folding funnel has been explored using segment wise Root Mean Square Deviation (RMSD) and Principal Component Analysis (PCA) as reaction coordinates. The combination of REMD and CGMD has helped to carry out very long time scales simulations where the results are close to the experimental findings. The present study is targeted to explore the folding funnel as well as to study the effect of temperature range in REMD simulations.
Centre for Development of Advanced Computing
Pune University Campus, Pune – 411 007, India